FDA approves repotrectinib for ROS1-positive non-small cell lung cancer

Regulatory approval: On Nov 15, 2023, the FDA approved repotrectinib (Augtyro) for locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC). The approval includes both ROS1 TKI–naïve patients and patients previously treated with a ROS1 tyrosine kinase inhibitor. Approval was based on the single-arm TRIDENT-1 trial, with confirmed ORR 79% in TKI-naïve patients and 38% in prior ROS1 inhibitor–treated patients; median DOR was 34.1 and 14.8 months, respectively.

FDA approval: repotrectinib for ROS1-positive NSCLC (Nov 15, 2023)

The FDA approved repotrectinib (Augtyro; Bristol-Myers Squibb Company) on November 15, 2023 for locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC).

This approval is reported as the first FDA approval in ROS1-positive NSCLC that includes patients previously treated with a ROS1 tyrosine kinase inhibitor (TKI), in addition to TKI-naïve patients.

Supporting evidence (TRIDENT-1)

Approval was based on TRIDENT-1 (NCT03093116), a global, multicenter, single-arm, open-label, multi-cohort trial. Efficacy was evaluated in:

  • 71 ROS1 TKI–naïve patients (allowed up to 1 prior line of platinum-based chemotherapy and/or immunotherapy)
  • 56 patients with 1 prior ROS1 TKI (no prior platinum-based chemotherapy or immunotherapy)

Primary efficacy measures were overall response rate (ORR) and duration of response (DOR) by RECIST v1.1, assessed by blinded independent central review.

  • Confirmed ORR: 79% (95% CI, 68–88) in TKI-naïve; 38% (95% CI, 25–52) after prior ROS1 inhibitor
  • Median DOR: 34.1 months (95% CI, 25.6–not evaluable) vs 14.8 months (95% CI, 7.6–not evaluable)

Responses were reported in intracranial lesions (measurable CNS metastases) and in patients with resistance mutations after TKI therapy.

Safety and dosing (label highlights)

Most common adverse reactions (>20%): dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, ataxia, fatigue, cognitive disorders, muscular weakness.

Recommended dose: 160 mg orally once daily (with or without food) for 14 days, then 160 mg twice daily until progression or unacceptable toxicity.

The application received priority review, breakthrough designation, and fast track designation.

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